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Studies of Fox01 in Insulin Resistance and its interaction with PPARgamma

Fox01 胰岛素抵抗及其与 PPARgamma 相互作用的研究

基本信息

批准号：
7803469
负责人：
JANE KIM
金额：
$ 0.11万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-20 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7803469
关键词：
Address Adenoviruses Adipocytes Adipose tissue Adult Affect Agonist Alleles Basic Science Biochemical Bone Marrow Transplantation Caenorhabditis elegans California Cell Cycle Regulation Cell Nucleus Cells Child Childhood Cues Cytoplasm DNA-Protein Interaction Data Deltastab Development Diabetes Mellitus Diet Disease Endocrinologist Environment Event Fatty acid glycerol esters Fellowship Funding Gene Expression Genes Genetic Genetic Epistasis Genetic Transcription Goals Histologic Homeostasis In Vitro Inflammation Insulin Insulin Resistance Invertebrates Knock-out Knockout Mice Laboratories Ligands Lipolysis Mammalian Cell Measures Mediating Mentors Metabolic Metabolic Control Metabolism Modeling Molecular Molecular Target Mouse Strains Mus Mutation Nature Non-Insulin-Dependent Diabetes Mellitus Nuclear Receptors Nutrient Obese Mice Obesity Overweight PPAR gamma Pathogenesis Pathway interactions Phosphorylation Physiological Physiology Play Principal Investigator Protein Isoforms Protein-Serine-Threonine Kinases Proteins Regulation Research Research Personnel Role Scientist Signal Transduction Site Solid Testing Therapeutic Training Transgenes Transgenic Mice Transgenic Model Universities Vertebrates Work adipocyte differentiation blood glucose regulation career extracellular forkhead protein gain of function glucose uptake improved in vivo in vivo Model insulin sensitivity insulin signaling lipid biosynthesis loss of function macrophage mouse model mutant novel postnatal programs promoter research study response skills transcription factor

项目摘要

DESCRIPTION (provided by applicant): The goals of the proposed training are two-fold: i) to provide training and mentoring to prepare Dr. Jane Kim for an independent research career in diabetes and insulin action and ii) to identify physiologically relevant mechanisms of signaling via the FoxOI forkhead transcription factor in the regulation of adipose metabolism. The principal investigator is a NIH-trained pediatric endocrinologist who has also completed a basic science research fellowship at Columbia University, NY. The proposed funding period will enable her to fully develop the research skills necessary to succeed as an independent investigator. Genetic and biochemical evidence from both vertebrate and invertebrate models indicate that FoxOI plays a pivotal role in insulin action. However, its signaling mechanism remains only partially understood. This proposal investigates the role of FoxOI in adipose tissue physiology. This work is particularly relevant to understanding the aberrant signaling events that underlie insulin resistance in diabetes and overweight/obesity, diseases that affect 65% of adults and 16.5% of children in the U.S. The trainee hypothesizes that FoxOI negatively regulates insulin action in adipocytes and that its effect may be explained, at least in part, by the alterations in PPARgamma-mediated signaling. The specific aims include: 1) using adenoviral expression of wild-type and mutant FoxOI transgenes in cultured adipocytes to define their effects on insulin action and to identify novel targets of FoxOI-dependent transcription; 2) investigating the in vivo role of FoxO proteins through the analysis of FoxOI and FoxO4 knockout mice; and 3) generating novel in vivo models with adipose-targeted mutations of FoxOI. These studies will be the first to comprehensively investigate the physiologic role of FoxOI in adipose tissue using complementary in vitro and in vivo approaches. Dr. Jerrold Olefsky will serve as a mentor for Dr. Kim's scientific development at the University of California, San Diego, and his laboratory will provide Dr. Kim with access to an exceptionally diverse intellectual and research environment. Dr. Olefsky is recognized as an outstanding mentor and leader in the field of insulin action and diabetes. This approach will provide Dr. Kim with a solid platform to construct a successful career as an independent scientist and academic pediatric endocrinologist.

描述（由申请人提供）：